The protein actin is implicated in various types of cellular functions. Many of the functions such as patching and capping of cell surface receptors, phagocytosis amoeboid movement and cellular adhesion to a substratum have been thought to involve an actin plasma membrane interaction. The interaction must occur on the cytoplasmic side of the membrane where actin is found. While indirect evidence for an actin-membrane association is available, direct evidence is lacking. In fact all of the above mentioned cellular functions could occur without such an interaction. A key to understanding these functions is determining if a direct and specific actin-plasma membrane association occurs. Specificity is used here to indicate the interaction of actin with a particular receptor in the membrane. Actin was dissociated from the cytoplasmic surface of the plasma membrane from Dicty-ostelium discoideum. The cytoplasmic surface was selectively exposed by isolating the membrane using cationic beads. When purified actin was added back to the membrane the amount that bound was proportional to the actin concentration. Trypsinization of the cytoplasmic surface abolished binding while chymotrypsin was only partly effective. Far more F-actin bound to the membrane than G-actin and the binding was not inhibited by cytochalasin B. The results support the hypothesis that actin specifically interacts with unique proteins exposed on the cytoplasmic surface of the plasma membrane.